The soluble rat lens protein has been successfully fractionated into 6 fractions, I-VI. Fractions I, III-IV and V have been identified as alpha, beta, and gamma crystallins, respectively. Fraction II, which is not identifiable as a component of the crystallins, comprises a novel group of proteins. Attempts are being made to isolate the two major proteins and one minor protein in the fraction with isoelectrofocusing and other methods. The physical, chemical and biological characteristics of each of the proteins can then be studied in detail. The rat gamma crystallin has been further fractionated into 6 subfractions, a-f, by ion exchange chromatography. Their molecular weights, amino acid composition, partial amino acid sequence and immunological properties are being investigated. In progress also are studies on the distribution and molecular weights of soluble normal (juvenile and adult) and cataract human lenses. Determination of the soluble high molecular weight aggregates in the cataract lens is being carried out. Efforts are also being devoted to the description and classification of the human cataract lenses utilizing physical and optical means. Both galactose- and x-ray-induced cataract in rat are being used as model experimental systems. This biochemical group and the electron microscopy group are jointly embarking on studies to relate biochemical functions and ultrastructure of the lens. It is hoped that the proteins in the lens can be extracted systematically and that the resulting changes in ultrastructure can be monitored concurrently.